@article{58d750cebda44c85ae963d2f1828f2b0,
title = "Scalable, multimodal profiling of chromatin accessibility, gene expression and protein levels in single cells",
abstract = "Recent technological advances have enabled massively parallel chromatin profiling with scATAC-seq (single-cell assay for transposase accessible chromatin by sequencing). Here we present ATAC with select antigen profiling by sequencing (ASAP-seq), a tool to simultaneously profile accessible chromatin and protein levels. Our approach pairs sparse scATAC-seq data with robust detection of hundreds of cell surface and intracellular protein markers and optional capture of mitochondrial DNA for clonal tracking, capturing three distinct modalities in single cells. ASAP-seq uses a bridging approach that repurposes antibody:oligonucleotide conjugates designed for existing technologies that pair protein measurements with single-cell RNA sequencing. Together with DOGMA-seq, an adaptation of CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) for measuring gene activity across the central dogma of gene regulation, we demonstrate the utility of systematic multi-omic profiling by revealing coordinated and distinct changes in chromatin, RNA and surface proteins during native hematopoietic differentiation and peripheral blood mononuclear cell stimulation and as a combinatorial decoder and reporter of multiplexed perturbations in primary T cells.",
author = "Mimitou, {Eleni P.} and Lareau, {Caleb A.} and Chen, {Kelvin Y.} and Zorzetto-Fernandes, {Andre L.} and Yuhan Hao and Yusuke Takeshima and Wendy Luo and Huang, {Tse Shun} and Yeung, {Bertrand Z.} and Efthymia Papalexi and Thakore, {Pratiksha I.} and Tatsuya Kibayashi and Wing, {James Badger} and Mayu Hata and Rahul Satija and Nazor, {Kristopher L.} and Shimon Sakaguchi and Ludwig, {Leif S.} and Sankaran, {Vijay G.} and Aviv Regev and Peter Smibert",
note = "Funding Information: We acknowledge support from the Broad Institute and the Whitehead Institute Flow Cytometry Core facilities. This research was supported by National Institutes of Health grants nos. R01 DK103794 (V.G.S.) and R01 HL146500 (V.G.S.); National Institutes of Health/National Human Genome Research Institute grants nos. R21 HG-009748 (P.S.) and RM1 HG0110014 (P.S.); Grants-in-Aid by the Japan Society for Promotion of Science for Specially Promoted Research no. 16H06295 (S.S.); the Japan Agency for Medical Research and Development for Leading Advanced Projects for Medical Innovation (S.S.); a gift from the Lodish Family to Boston Children{\textquoteright}s Hospital (V.G.S.); the New York Stem Cell Foundation (NYSCF) (V.G.S.); the Howard Hughes Medical Institute and Klarman Cell Observatory (A.R.); and the Chan Zuckerberg Initiative/ Silicon Valley Community Foundation Human Cell Atlas grant no. HCA3-0000000309 (P.S.). V.G.S. is an NYSCF Robertson Investigator. C.A.L. is supported by a Stanford Science Fellowship. L.S.L is supported by an Emmy Noether fellowship by the German Research Foundation (LU 2336/2-1). Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2021",
month = oct,
doi = "10.1038/s41587-021-00927-2",
language = "English (US)",
volume = "39",
pages = "1246--1258",
journal = "Nature Biotechnology",
issn = "1087-0156",
publisher = "Nature Publishing Group",
number = "10",
}